BACKGROUND: The current requirement is to establish the preoperative diagnosis accurately as possible and to achieve an adequate extent of surgery. The aim of this study was to define the preoperative clinical and molecular genetic risks of malignancy in indeterminate thyroid nodules (Bethesda III and IV) and to determine their impact on the surgical strategy. METHODS: Prospectively retrospective analysis of 287 patients provided the basis of preoperative laboratory examination, sonographic stratification of malignancy risks and cytological findings. Molecular tests focused on pathogenic variants of genes associated with thyroid oncogenesis in cytologically indeterminate nodules (Bethesda III and IV). The evaluation included clinical risk factors: positive family history, radiation exposure and growth in size and/or number of nodules. RESULTS: Preoperative FNAB detected 52 cytologically indeterminate nodules (28.7%) out of 181 patients. Postoperative histopathological examination revealed malignancy in 12 cases (23.7%) and there was no significant difference between Bethesda III and IV categories (P=0.517). Clinical risk factors for malignancy were found in 32 patients (61.5%) and the presence of at least one of them resulted in a clearly higher incidence of malignancy than their absence (31.3% vs. 10.0%, respectively). Pathogenic variants of genes were detected in 12/49 patients in Bethesda III and IV, and in 4 cases (33.3%) thyroid carcinoma was revealed. The rate of malignancies was substantially higher in patients with pathogenic variants than in those without (33.3% vs. 16.2%, respectively). CONCLUSIONS: Our experience implies that molecular genetic testing is one of several decision factors. We will continue to monitor and enlarge our patient cohort to obtain long-term follow-up data.

• MeSH
• Adult MeSH
• Genetic Testing MeSH
• Middle Aged MeSH
• Humans MeSH
• Thyroid Neoplasms * genetics   MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Aged MeSH
• Biopsy, Fine-Needle MeSH
• Thyroid Nodule * genetics   pathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

OBJECTIVES: To determine the safety and oncological advantages of en bloc resection of bladder tumour (ERBT) vs conventional transurethral resection of bladder tumour (cTURBT) in terms of resection quality, staging quality, and safety. PATIENTS AND METHODS: We conducted a single-blinded randomised controlled trial at seven European hospitals with the following inclusion criteria: first diagnosis of non-muscle-invasive bladder cancer, no singular carcinoma in situ, and tumour size >4.3 mm. Patients were randomised intraoperatively in a 1:1 ratio to either the ERBT or cTURBT group. Outcome analysis was performed using the chi-square test, t-test, and multivariate regression analysis. RESULTS: A total of 97 patients were randomised into the study (cTURBT = 40, ERBT = 57). A switch to cTURBT was necessary in two patients (3.5%) and 11.5% of the screened patients were preoperatively excluded for ERBT. There was no difference in the specimen presence of detrusor muscle with 73.7% in cTURBT and 67.3% in ERBT specimens (P = 0.69). There were no significant differences in mean operative time (ERBT 27.6 vs cTURBT 25.4 min, P = 0.450) or mean resection time (ERBT 16.3 vs cTURBT 15.5 min, P = 0.732). Overall the complication rate did not differ significantly (ERBT 18.2% vs cTURBT 7.5%, P = 0.142). Bladder perforations occurred significantly more often in the ERBT group (ERBT seven vs cTURBT none, P = 0.020). R0 status was reported more often after ERBT, whilst a second resection was significantly less frequent after ERBT (P = 0.018). Recurrence rates were comparable for both techniques after 6 months of follow-up. CONCLUSION: The feasibility of ERBT is higher than previously reported. Whereas other perioperative and safety parameters are comparable to cTURBT, bladder perforations occurred significantly more often in the ERBT group and raised safety concerns. This is why this trial was terminated.

• MeSH
• Cystectomy * methods   adverse effects   MeSH
• Single-Blind Method MeSH
• Carcinoma, Transitional Cell surgery   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Urinary Bladder Neoplasms * surgery   pathology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Transurethral Resection of Bladder MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH

BACKGROUND AND OBJECTIVE: While prostate cancer (PCa) incidence and mortality rates continue to rise, early detection of PCa remains highly controversial, and the research landscape is rapidly evolving. Existing systematic reviews (SRs) and meta-analyses (MAs) provide valuable insights, but often focus on single aspects of early detection, hindering a comprehensive understanding of the topic. We aim to fill this gap by providing a comprehensive SR of contemporary SRs covering different aspects of early detection of PCa in the European Union (EU) and the UK. METHODS: On June 1, 2023, we searched four databases (Medline ALL via Ovid, Embase, Web of Science, and Cochrane Central Register of Controlled Trials) and Google Scholar. To avoid repetition of previous studies, only SRs (qualitative, quantitative, and/or MAs) were considered eligible. In the data, common themes were identified to present the evidence systematically. KEY FINDINGS AND LIMITATIONS: We identified 1358 citations, resulting in 26 SRs eligible for inclusion. Six themes were identified: (1) invitation: men at general risk should be invited at >50 yr of age, and testing should be discontinued at >70 yr or with <10 yr of life expectancy; (2) decision-making: most health authorities discourage population-based screening and instead recommend a shared decision-making (SDM) approach, but implementation of SDM in clinical practice varies widely; decision aids help men make more informed and value-consistent screening decisions and decrease men's intention to attempt screening, but these do not affect screening uptake; (3) acceptance: facilitators for men considering screening include social prompting by partners and clinician recommendations, while barriers include a lack of knowledge, low-risk perception, and masculinity attributes; (4) screening test and algorithm: prostate-specific antigen-based screening reduces PCa-specific mortality and metastatic disease in men aged 55-69 yr at randomisation if screened at least twice; (5) harms and benefits: these benefits come at the cost of unnecessary biopsies, overdiagnosis, and subsequent overtreatment; and (6) future of screening: risk-adapted screening including (prebiopsy) risk calculators, magnetic resonance imaging, and blood- and urine-based biomarkers could reduce these harms. To enable a comprehensive overview, we focused on SRs. These do not include the most recent prospective studies, which were therefore incorporated in the discussion. CONCLUSIONS AND CLINICAL IMPLICATIONS: By identifying consistent and conflicting evidence, this review highlights the evidence-based foundations that can be built upon, as well as areas requiring further research and improvement to reduce the burden of PCa in the EU and UK. PATIENT SUMMARY: This review of 26 reviews covers various aspects of prostate cancer screening such as invitation, decision-making, screening tests, harms, and benefits. This review provides insights into existing evidence, highlighting the areas of consensus and discrepancies, to guide future research and improve prostate cancer screening strategies in Europe.

• MeSH
• Early Detection of Cancer * MeSH
• European Union * MeSH
• Humans MeSH
• Prostatic Neoplasms * diagnosis   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Geographicals
• United Kingdom MeSH

A new group of potent histone deacetylase inhibitors (HDACis) capable of inhibiting cell growth and affecting cell-cycle progression in Tohoku Hospital Pediatrics-1 (THP-1) monocytic leukaemia cells was synthesized. The inhibitors belong to a series of hydroxamic acid derivatives. We designed and synthesized a series of 22 N-hydroxycinnamamide derivatives, out of which 20 are new compounds. These compounds contain various substituted anilides as the surface recognition moiety (SRM), a p-hydroxycinnamate linker, and hydroxamic acids as the zinc-binding group (ZBG). The whole series of synthesized hydroxamic acids inhibited THP-1 cell proliferation. Compounds 7d and 7p, which belong to the category of derivatives with the most potent antiproliferative properties, exert a similar effect on cell-cycle progression as vorinostat and induce apoptosis in THP-1 cells. Furthermore, compounds 7d and 7p were demonstrated to inhibit HDAC class I and II in THP-1 cells with comparable potency to vorinostat and increase acetylation of histones H2a, H2b, H3, and H4. Molecular modelling was used to predict the probable binding mode of the studied HDACis in class I and II histone deacetylases in terms of Zn2+ ion chelation by the hydroxamate group.

• MeSH
• Apoptosis * drug effects   MeSH
• Cell Cycle drug effects   MeSH
• Histone Deacetylases metabolism   MeSH
• Histone Deacetylase Inhibitors * pharmacology   chemical synthesis   chemistry   MeSH
• Hydroxamic Acids * pharmacology   chemical synthesis   chemistry   MeSH
• Coumaric Acids * pharmacology   chemistry   chemical synthesis   MeSH
• Humans MeSH
• Molecular Structure MeSH
• Cell Line, Tumor MeSH
• Cell Proliferation drug effects   MeSH
• Antineoplastic Agents * pharmacology   chemical synthesis   chemistry   MeSH
• Drug Screening Assays, Antitumor MeSH
• Molecular Docking Simulation MeSH
• THP-1 Cells MeSH
• Dose-Response Relationship, Drug MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

• Keywords
• studie Lipidica, lipidotomický test,
• MeSH
• Early Detection of Cancer methods   MeSH
• Hematologic Tests MeSH
• Clinical Studies as Topic MeSH
• Plasma MeSH
• Humans MeSH
• Lipids blood   MeSH
• Multicenter Studies as Topic MeSH
• Biomarkers, Tumor MeSH
• Pancreatic Neoplasms * diagnosis   prevention & control   MeSH
• Primary Health Care MeSH
• Check Tag
• Humans MeSH

Nádory močového měchýře představují celosvětově časté onemocnění. Mnohdy se jedná o recidivující nádory s nutností dlouhodobého sledování, což z nich činí nádory s vysokou prevalencí. Základní diagnostickou metodou je cystoskopie, která je nezbytná i v rámci sledování. V obou případech, v diagnostice i dispenzarizaci, tedy využíváme invazivní metodu s nezanedbatelným rizikem komplikací. Jediným doporučeným neinvazivním vyšetřením je cytologie moči. Limitace cystoskopie a cytologie moči motivují výzkum celé řady neinvazivních biomarkerů detekovaných v moči s cílem nalezení dostatečně senzitivního a specifického vyšetření, které by bylo možné využít nejen v diagnostice a sledování nádorů močového měchýře. Doposud bylo na trh uvedeno několik biomarkerů vyskytujících se v přítomnosti nádorového postižení močového měchýře. V článku jsou představeni hlavní zástupci neinvazivních biomarkerů a jejich možné využití.

Major statement: Non-invasive urinary biomarkers represent a promising alternative to cur- rent diagnostic methods for bladder cancer. This study aims to present the main available biomarkers, evaluate their benefits, and assess their potential use in diagnosis and patient monitoring.Summary: Bladder tumors are a common disease worldwide. They are often recurrent tumors requiring long-term monitoring, making them highly prevalent. The primary diagnostic method is cystoscopy, which is also essential for follow-up. In both cases - diagnosis and surveillance - an invasive method is used, carrying a significant risk of complications. The only recommended non-invasive examination is urine cytology. The limitations of cystoscopy and urine cytology drive research into various non-invasive urinary biomarkers to find a test that is sufficiently sensitive and specific for use not only in diagnosing but also in monitoring bladder tumors. Several biomarkers associated with bladder cancer have already been introduced to the market. This article presents the main representatives of non-invasive biomarkers and their potential applications.

• MeSH
• Early Detection of Cancer MeSH
• Cystoscopy MeSH
• Cytodiagnosis MeSH
• Humans MeSH
• Urine cytology   MeSH
• Biomarkers, Tumor analysis   MeSH
• Neoplasm Proteins MeSH
• Urinary Bladder Neoplasms * surgery   diagnosis   pathology   MeSH
• Check Tag
• Humans MeSH

BACKGROUND: The treatment of non-small cell lung cancer (NSCLC) patients is correlated with the efficacy of immune checkpoint blockade therapy (ICB) targeting programmed cell death ligand 1 (PD-L1) or its cognate receptor (PD-1) on cancer cells or infiltrating immune cells. Analysis of PD-L1/PD-1 expression in tumor tissue represents a crucial step before PD-L1/PD-1 blocker usage. METHODS: We used directed evolution of protein variants derived from a 13 kDa Myomedin loop-type combinatorial library with 12 randomized amino acid residues to select high-affinity binders of human PD-L1 (hPD-L1). After the ribosome display, individual clones were screened by ELISA. Detailed analysis of binding affinity and kinetics was performed using LigandTracer. The specificity of Myomedins was assessed using fluorescent microscopy on HEK293T-transfected cells and cultured cancer cells in vitro, formalin-fixed paraffin-embedded (FFPE) sections of human tonsils, and FFPE tumor samples of NSCLC patients. RESULTS: Seven identified PD-L1 binders, called MLE, showed positive staining for hPD-L1 on transfected HEK293T cells and cultured MCF-7 cells. MLE031, MLE105, MLE249, and MLE309 exhibited high affinity to both human and mouse PD-L1-transfected HEK293T cells measured with LigandTracer. The diagnostic potential of MLE variants was tested on human tonsillitis tissue and compared with diagnostic anti-PD-L1 antibody DAKO 28-8 and PD-L1 IHC 22C3 pharmDx antibody. MLE249 and MLE309 exhibited an excellent overlap with diagnostic DAKO 28-8 (Pearson ́s coefficient (r) = 0.836 and 0.731, respectively) on human tonsils on which MLE309 exhibited also excellent overlap with diagnostic 22C3 antibody (r = 0.876). Using three NSCLC tissues, MLE249 staining overlaps with 28-8 antibody (r = 0.455-0.883), and MLE309 exhibited overlap with 22C3 antibody (r = 0.534-0.619). Three MLE proteins fused with Fc fragments of rabbit IgG, MLE249-rFc, MLE309-rFc and MLE031-rFc, exhibited very good overlap with anti-PD-L1 antibody 28-8 on tonsil tissue (r = 0.691, 0.610, and 0.667, respectively). Finally, MLE249-rFc, MLE309-rFc and MLE031-rFc exhibited higher sensitivity in comparison to IHC 22C3 antibody using routine immunohistochemistry staining system Ventana, which is one of gold standards for PD-L1 diagnosis. CONCLUSIONS: We demonstrated the development of MLE Myomedins specifically recognizing hPD-L1 that may serve as a refinement tool for clinical PD-L1 detection.

• MeSH
• B7-H1 Antigen * metabolism   MeSH
• HEK293 Cells MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Lung Neoplasms * diagnosis   metabolism   pathology   MeSH
• Carcinoma, Non-Small-Cell Lung * diagnosis   metabolism   pathology   MeSH
• Protein Binding MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Prostate cancer (PCa) poses a significant global health threat, with high incidence and mortality rates. In 2022, the Council of the European Union (EU) updated its screening recommendations, prioritizing PCa screening. This signals a crucial step towards establishing new early detection programmes in EU member states. This study investigates the role of policy makers and governance in cancer screening to inform the development of PCa screening. We had a mixed-method study design. First, a rapid review was conducted on policy making and governance in EU-funded cancer screening initiatives. Second, a focus group discussion reviewed study concepts and methods. Third, a systematic literature review was performed and, fourth, a series of in-depth interviews with actors involved in PCa screening pilots was conducted. Data were analysed thematically and the findings are used to propose 10 recommendations for policy makers. The results of the rapid review and focus group discussion framed the study in the context of existing cancer screening programmes across the EU, and highlighted what already exists in terms of governance tools and methodology. The literature review and in-depth interviews presented key learnings from the literature and real-life settings. These findings are reported using a pre-existing conceptional framework for effective health system governance. The study underscores the critical importance of governance in effective cancer screening programmes. Ten recommendations are proposed, including: defining cancer screening governance, allocating budgets and defining common approaches and key performance indicators for evaluation, establishing methods to enhance citizen participation, and reinforcing network governance.

• MeSH
• Early Detection of Cancer * methods   MeSH
• European Union MeSH
• Humans MeSH
• Prostatic Neoplasms * diagnosis   MeSH
• Mass Screening * organization & administration   MeSH
• Administrative Personnel * MeSH
• Policy Making * MeSH
• Health Policy * MeSH
• Focus Groups MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Systematic Review MeSH

A series of triterpenoids of the lupane, taraxastane, friedelane and baccharane type were oxidized using selenium dioxide (SeO2) and benzeneseleninic anhydride (BSA) under various conditions. Depending on the reaction conditions, different reaction pathways were observed, including dehydrogenation, allylic oxidation, and 1,2-diketone formation. In this way, derivatives functionalized in the triterpene core (especially in rings A, D, and E), difficult to obtain by other methods, can be easily prepared. In some cases, rarely observed α-phenylseleno-ketones were isolated. An unexpected reaction involving the cleavage of the carbon-carbon double bond was observed in the presence of stoichiometric amounts of osmium tetroxide. Further transformations of selected intermediates facilitated the synthesis of new, functionally enriched derivatives. The key reaction pathways were investigated using density functional theory (DFT), focusing on bond length variations and transition states, revealing energetically favored pathways and critical transition structures, including covalent and noncovalent interactions. Solvent and isomerization equilibrium effects were proposed to explain the experimentally observed discrepancies. Cytotoxic activity of selected derivatives was investigated. Derivatives 4 and 38 showed strongest cytotoxicity in cancer cells and fibroblasts (IC50 2.6-26.4 μM); some compounds were selective for G-361 or HeLa cells. These results suggest that they may find application in pharmaceuticals.

• MeSH
• Humans MeSH
• Molecular Structure MeSH
• Cell Line, Tumor MeSH
• Oxidation-Reduction MeSH
• Pentacyclic Triterpenes MeSH
• Cell Proliferation drug effects   MeSH
• Antineoplastic Agents * pharmacology   chemistry   chemical synthesis   MeSH
• Drug Screening Assays, Antitumor MeSH
• Selenium * chemistry   MeSH
• Density Functional Theory MeSH
• Triterpenes * chemistry   pharmacology   chemical synthesis   MeSH
• Dose-Response Relationship, Drug MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Current European/US guidelines recommend that molecular testing in advanced non-small cell lung cancer (aNSCLC) be performed using next-generation sequencing (NGS). However, the global uptake of NGS is limited, largely owing to reimbursement constraints. We compared real-world costs of NGS and single-gene testing (SGT) in nonsquamous aNSCLC. This observational study was conducted across 10 pathology centers in 10 different countries worldwide. Biomarker data collected via structured questionnaires (1 January-31 December 2021) were used to feed micro-costing analyses for three scenarios ['Starting Point' (SP; 2021-2022), 'Current Practice' (CP; 2023-2024), and 'Future Horizons' (FH; 2025-2028)] in both a real-world model, comprising all biomarkers tested by each center, and a standardized model, comprising the same sets of biomarkers across centers. Testing costs (including retesting) encompassed personnel costs, consumables, equipment, and overheads. Overall, 4,491 patients with aNSCLC were evaluated. Mean per-patient costs decreased for NGS relative to SGT over time, with real-world model costs 18% lower for NGS than for SGT in the SP scenario, and 26% lower for NGS than for SGT in the CP scenario. Mean per-biomarker costs also decreased over time for NGS relative to SGT. In the standardized model, the tipping point for the minimum number of biomarkers required for NGS to result in cost savings (per patient) was 10 and 12 in the SP and CP scenarios, respectively. Retesting had a negligible impact on cost analyses, and results were robust to variation in cost parameters. This study provides robust real-world global evidence for cost savings with NGS-based panels over SGT to evaluate predictive biomarkers in nonsquamous aNSCLC when the number of biomarkers to be tested exceeds 10. Widespread adoption of NGS may enable more efficient use of limited healthcare resources.

• MeSH
• Cost-Benefit Analysis MeSH
• Genetic Testing economics   methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor * genetics   MeSH
• Lung Neoplasms * genetics   pathology   diagnosis   MeSH
• Health Care Costs MeSH
• Carcinoma, Non-Small-Cell Lung * genetics   diagnosis   pathology   MeSH
• Aged MeSH
• High-Throughput Nucleotide Sequencing * economics   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH
• Comparative Study MeSH