Radiology and Oncology最新文献

Background: Electroporation-based therapies are being explored in glioblastoma (GB) treatment, as means of enhancing drug delivery or achieving nonthermal ablation. Yet, little is known about how sublethal exposure affects the invasive behaviour of GB tumour cells.

Materials and methods: Five patient-derived GB cell lines were initially screened for intrinsic invasive potential, and two most invasive (NIB140 CORE and NIB216 CORE) were selected for further experiments with electroporation treatment. Cells in suspension were exposed to bursts of high-frequency biphasic electric pulses resulting in electric field strength of 1 kV/cm, which corresponded to conditions of reversible electroporation. Changes in cell invasion and gene regulation were assessed 24 hours after electroporation using transwell assay and RNA transcriptome analysis, respectively.

Results: Reversible electroporation at 1.0 kV/cm enhanced invasion in a cell line-dependent manner. NIB140 CORE showed a consistent and pronounced increase, with a median of 3.74-fold (274%) higher number of invading cells compared to sham control. In contrast, NIB216 CORE exhibited only a modest increase in invasion (1.30-fold; 30%). Transcriptomic profiling identified modulation of genes linked to extracellular matrix organization and ion channel activity in NIB140 CORE, and cytoskeletal remodelling in NIB216 CORE, indicating the activation of invasion-related pathways.

Conclusions: These findings highlight a potential risk of pro-invasive responses in GB cells. In tumour ablation with irreversible electroporation, this concern relates to cells in the peripheral zone that may experience only sublethal electric fields, while in electrochemotherapy, a similar risk may arise if permeabilized cells are not effectively eliminated due to insufficient local drug delivery. Nevertheless, the two tested cell lines responded differently, underscoring patient-specific heterogeneity and the need for validation in more physiologically relevant models.

Background: Low skeletal muscle mass has been increasingly recognized as a negative prognostic factor in oncology. According to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), sarcopenia is defined as a progressive and generalized skeletal muscle disorder characterized by the loss of muscle strength and muscle mass, which can lead to impaired physical performance. This study aimed to investigate whether baseline low muscle mass and dynamic changes in muscle mass during immunotherapy could predict treatment response and survival in patients with metastatic renal cell carcinoma (mRCC) treated with Nivolumab.

Patients and methods: This retrospective cohort study included 50 mRCC patients (35 men, 15 women; mean age 59.1 ± 10.2 years) who received Nivolumab between 2019 and 2022 and underwent abdominal computed tomography (CT) before and during treatment. Muscle mass was assessed by calculating the skeletal muscle index (SMI) at the third lumbar vertebra using standard Hounsfield unit thresholds (-29 to +150 HU). Treatment response was evaluated according to immune Response Evaluation Criteria in Solid Tumors (iRECIST). Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves and Cox regression models.

Results: Low muscle mass was identified in 60% of patients and was significantly associated with multiple organ metastases (p = 0.003). Patients with baseline low muscle mass or a negative change in SMI during treatment demonstrated poorer treatment response (p = 0.027 and p = 0.021, respectively). Both OS and PFS were significantly shorter in patients with low muscle mass and those with declining muscle mass during treatment.

Conclusions: Pre-treatment low muscle mass and muscle mass decline during immunotherapy were independently associated with inferior survival and treatment response in mRCC patients receiving Nivolumab. CT-based muscle mass assessment may serve as an imaging-based prognostic biomarker in this population.

Background: Pharyngeal squamous cell carcinoma (PSCC) is a significant health concern, with human papillomavirus 16 (HPV16) playing a key role in the etiology of oropharyngeal squamous cell carcinoma (OPSCC). HPV16-related OPSCC exhibits enhanced radiosensitivity compared to HPV16-unrelated PSCC, yet the underlying mechanisms remain poorly understood. As HPV16 oncoproteins E6 and E7 are known to interfere with innate immune signaling, we investigated how modulation of cytosolic DNA sensing pathways and innate immune responses changes after irradiation (IR) and whether this contributes to enhanced radiosensitivity in HPV16-related OPSCC.

Materials and methods: Using HPV16-related and -unrelated PSCC models, we examined baseline expression levels of DNA sensors and cytokines and assessed the effects of IR on double-stranded DNA (dsDNA) accumulation, activation of cytosolic DNA sensors, cytokines, and immune cell infiltration both in vitro and in vivo. Analyses were performed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescent staining.

Results: HPV16-related OPSCC exhibited a distinct baseline expression profile of DNA sensors and cytokines, consistent with suppression of the stimulator of interferon genes (STING) pathway. While IR-induced activation of DNA sensors was dose- and time-dependent across models, HPV16-related OPSCC showed selective activation of cyclic GMP-AMP synthase (cGAS) and STING without significant cytokine upregulation or immune activation. In contrast, HPV16-related and unrelated PSCCs displayed activation of multiple DNA sensors, increased cytokine expression, and enhanced immune cell infiltration following IR.

Conclusions: The key finding was that the involvement of cytosolic DNA sensing pathways and innate immune system do not increase radiosensitivity of HPV16-related OPSCC. In PSCC models, DNA sensor and cytokine expression varied depending on IR dose and fractionation.

Background: The study aimed to investigate cardiotoxicity among individuals undergoing anti-human epidermal growth factor receptor 2 (HER2) therapy with a low-to-moderate risk of cardiovascular complications. Cardiac magnetic resonance (CMR) imaging was employed in the investigation.

Patients and methods: HER2-positive breast cancer patients who underwent CMR examinations both before and during therapy (first follow-up: 3-5 months; second follow-up: 6-12 months) between January 2021 and December 2022 were prospectively included. Each patient was evaluated for the risk of cardiovascular toxicity.

Results: Thirty-five HER2-positive breast cancer patients were included (48.86 ± 10.34 years). Eighty-nine percent of patients had low cardiovascular toxicity risk, and 11% had moderate cardiovascular toxicity risk. At follow-up CMR, nine (25.71%) patients developed cardiac dysfunction. At follow-up 1, there was a notable decrease in left ventricular ejection fraction, stroke volume index, cardiac output index, and absolute strain values, accompanied by higher T1 and T2 values as well as end-systolic volume index compared to baseline (p ≤ 0.002). At follow-up 2, the T1 and T2 values recovered to near baseline. The cardiac output index exhibited a continuous decline (p ≤ 0.022), while other variables were similar (p > 0.05). Furthermore, at follow-up 1, the T1 value displayed a marked increase in patients with 1-3 points in cardiovascular toxicity risk factors compared to those with no risk factors (p ≤ 0.043).

Conclusions: It is common for patients with low-to-moderate cardiovascular risk to experience early cardiotoxicity during anti-HER2 therapy. T1 mapping was a valuable approach for quantifying the specific extent of subtle tissue damage.

Background: This article compares the real-world performance and safety of the three transcatheter aortic valve implantation (TAVI) platforms: Myval, Sapien, and Evolut in patients with severe symptomatic aortic stenosis and low to moderate surgical risk.

Patients and methods: Between September 2019 and September 2023, 1053 TAVI procedures were performed in the University Medical Centre Ljubljana, Slovenia. We used propensity-score match analysis to compare the Myval, Sapien, and Evolut platforms. 180 patients were enrolled in the propensity-score matching study, 60 for each platform. The study endpoints included haemodynamic outcomes compared to baseline, in-hospital clinical safety outcomes, and all-cause mortality at 30 days and one year.

Results: Changes in peak aortic valve velocity, mean aortic gradient, effective orifice area, and left ventricular ejection fraction were comparable between the platforms. After propensity score matching (tri-match), the rates of stroke (3.4% vs. 3.4% vs. 0.0%, p = 0.548), life-threatening bleeding (1.7% vs. 1.7% vs. 1.7 %), periprocedural myocardial infarction (3.3% vs. 0.0% vs. 0.0%, p = 0.330), postprocedural permanent pacemaker implantation rate (11.9% vs. 10.2% vs. 15.0%, p = 0.719), all-cause mortality at 30 days (3.3% vs. 5.0% vs. 3.3%; p = 1.000) and at 1 year (8.3% vs. 8.3% vs. 10.0%, p = 0.934) were comparable between the Myval, Sapien, and Evolut series, respectively. 2 cases of moderate paravalvular regurgitation were reported, one in Myval, and one in Sapien series.

Conclusions: The tri-match analysis of the real-world aortic stenosis patients with low to moderate surgical risk treated with the Myval, Sapien, and Evolut series showed comparable performance, safety, efficacy, and survival.

Background: To test the hypothesis that clinical tumor response after a single cycle of induction chemotherapy (ICT) can reliably differentiate between chemo-/radiosensitive and resistant tumors in the larynx preservation setting.

Patients and methods: Treatment consisted of docetaxel/cisplatin/5-fluorouracil (TPF) ICT followed by concurrent chemoradiotherapy (cCRT) with weekly cisplatin. The response of the primary tumor was assessed by transnasal endoscopy after the first ICT cycle.

Results: 37/39 (95%) patients with laryngeal (46%) or hypopharyngeal (54%) carcinoma responded to one cycle of ICT, and two patients were referred for salvage surgery. Laryngectomy-free survival at 2 and 5 years was 87% and 75%, respectively. The corresponding rates for locoregional control (and also for disease-free survival) were 79% and 70% and for overall survival 92% and 82%.

Conclusions: Clinical assessment of tumor response to one cycle of TPF ICT serves as a valid and easy-to-use predictor of tumor sensitivity to platinum-based cCRT.

Background: Glioblastoma stem-like cells (GSCs) contribute to the resistance of glioblastoma (GBM) tumors to standard therapies. The background of the resistance of GSCs to the chemotherapeutic agent temozolomide is not yet fully understood in the context of cellular metabolism and the role of mitochondria. The aim of this study was to perform a detailed ultrastructural characterization of the mitochondria of GSCs prior and post temozolomide exposure and to compare it to differentiated GBM cells.

Materials and methods: Patient-derived and established GBM cell lines were used for the study. The ultrastructure of the mitochondria of the examined cell lines was assessed by transmission electron microscopy. The microscopic analysis was complemented and compared by an analysis of cell metabolism using Seahorse extracellular flux analysis.

Results: We found that the metabolic profile of GSCs is quiescent and aerobic. Their elongated mitochondria with highly organized cristae are indicating increased biogenesis and mitochondrial fusion and corresponds to a more oxidative phosphorylation (OXPHOS)-dependent metabolism. The metabolism of GSCs is dependent on OXPHOS and there are no changes in defective mitochondria fraction after the treatment with temozolomide. In contrast, differentiated GBM cells with fragmented mitochondria, which have less organized cristae, are more energetic and glycolytic. Temozolomide treatment induced ultrastructural mitochondrial damage in differentiated GBM cells.

Conclusions: We demonstrated differences in mitochondrial ultrastructure and cellular metabolism between GSCs and differentiated GBM cells in response to temozolomide, suggesting that mitochondria play an important role in the resistance of GSCs to temozolomide. This study provides a basis for further studies addressing GSC chemotherapy resistance in the context of mitochondrial structure and function.

Background: Focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase, plays a crucial role in focal adhesion turnover by interfacing between the extracellular space, transmembrane integrins, and actin filaments. Its significance for the progression of several malignancies, including bladder cancer, has been well-documented. However, its precise role and the implications of its inhibition in bladder cancer tissues and urothelial in vitro models has not been fully explored. This study examined FAK expression and function in human bladder cancer biopsies and in vitro bladder cancer models.

Materials and methods: Ex vivo analyses were performed using reverse transcription-quantitative PCR (qRT-PCR), western blotting, and immunohistochemistry to compare FAK expression between bladder cancer tissues and adjacent normal tissues. In vitro, FAK expression was assessed in low-grade (LG) human non-invasive papilloma urothelial cell line RT4 for NMIBC (Ta), high-grade (HG) human muscle-invasive cancer urothelial cell line T24 for MIBC (T2) and normal porcine urothelial (NPU) cells using qRT-PCR and western blotting, as well as flow cytometry for the quantification of FAK-positive RT4 and T24 cells. The role of FAK in cancer cell survival was explored in vitro using microRNA (miRNA) to silence FAK expression. Additionally, we used FAK inhibitors PND-1186, PF-573228 and defactinib to investigate the effects of FAK inhibition on normal compared to cancerous bladder urothelial cells.

Results: Ex vivo analyses demonstrated significantly higher FAK expression in bladder cancer tissues compared to adjacent normal tissues. Similarly, in vitro analyses showed significantly higher FAK expression in RT4 and T24 cells than NPU cells. Silencing FAK using anti-FAK plasmids led to increased caspase-3-mediated apoptosis of RT4 and T24 cells and growth reduction of stably transfected T24 cells. Importantly, based on cell viability assays, treatment with 100 μM defactinib for 2 hours per day on 3 consecutive days was identified as a clinically relevant regimen. Under this treatment, the viability of differentiated NPU cells remained high at 108.4 ± 17.1%, while the viability of 2-day RT4 and 2-day T24 cells was drastically reduced to 4.1 ± 2.7% and 7.6 ± 2.9%, respectively.

Conclusions: To our knowledge, this is the first report demonstrating the role of FAK and its inhibition across both normal and cancerous bladder urothelial models. This study highlights the critical role of FAK in the progression of human bladder cancer and establishes a foundation for exploring FAK inhibition as a potential therapeutic approach in bladder cancer treatment.

Background: Robotic platforms are increasingly employed in the field of minimally invasive pancreatic surgery. It is essential to develop an innovative method that ensures both safety and efficacy, producing outcomes comparable to those of established treatment modalities. Implementation process should incorporate surgical science, education, local implementation, and non-technical skills. In our study, we describe the safe implementation of a robotic platform in pancreatic surgery within our medical institution.

Patients and methods: We analysed prospectively collected data from the first ten consecutive robotic-assisted distal pancreatectomies (RDP) and pancreatoduodenectomies (RPD). Due to nature of the study basic statistical analysis were performed.

Results: The mean operating time was 211minutes (±49.4) for RDP and 365 minutes (±69.6) for RPD, with blood loss 330 mL for RDP and 195 mL for RPD. Hospital stay was 8.7 days (±3.9) in RDP and 7.9 days (±3.9) in RPD. One patient (10%) in the RDP group developed clinically relevant postoperative pancreatic fistula (CR-POPF) and delayed gastric emptying (DGE). The mean tumour size was 31 mm (±9.8) in the RDP and 27 mm (±7.5) in the RPD. The mean number of lymph nodes harvested was 6 (0-24) in the RDP and 15 (6-22) in the RPD. The R0 resection rate was 60% in the RDP and 70% in the RPD.

Conclusions: Robotic surgical technology can be safely and effectively integrated into a clinical setting. This integration should be facilitated through a well-established training program and curriculum. Nonetheless, patient selection is important, especially in the early phases of robotic program development.

Background: This epidemiological study aims to assess the cancer risk potentially associated with environmental exposure resulting from cement production and waste co-incineration at the Anhovo cement plant in Western Slovenia and to develop a strong and reliable methodological framework for the long-term surveillance of environmentally related cancer risks in small geographical areas.

Materials and methods: We integrated all the available data sources: cancer cases from the population-based Slovenian Cancer Registry; background population; and available measurements on exposure to air PM₁₀ particles and chromium (Cr) in the soil in the municipality of Kanal and the wider Goriška region. Relative risks of cancer in small geographical areas were estimated using Bayesian hierarchical spatial models and the population attributable fractions of the modelled risk factors were calculated. The point source analysis compared the cancer risk near the cement plant to that in more distant areas.

Results: The analysis did not reveal any excess cancer incidence in the area of the Anhovo cement plant or an association with the PM₁₀ particles and Cr in the soil. The incidence of mesothelioma remains high in the region, but stable in the last two decades.

Conclusions: In view of the environmental pollution caused by either historical cement production or the potential impact of current waste co-incineration activities in Kanal, we strongly recommend that a follow-up epidemiological study be carried out in the next 10 to 20 years. The methodological framework established in the present study provides a foundation for the ongoing surveillance of the cancer burden in the region.