Electron-Beam-Induced Grafting of Chitosan onto HDPE/ATZ Composites for Biomedical Applications.

The surface functionalisation of high-density polyethylene (HDPE) and HDPE/alumina-toughened zirconia (ATZ) surfaces with chitosan via electron-beam (EB) irradiation technique was exploited for preparing materials suitable for biomedical purposes. ATR-FTIR analysis and wettability measurements were employed for monitoring the surface changes after both irradiation and chitosan grafting reaction. Interestingly, the presence of ATZ loadings beyond 2 wt% influenced both the EB irradiation process and the chitosan functionalisation reaction, decreasing the oxidation of the surface and the chitosan grafting. The EB irradiation induced an increase in Young's modulus and a decrease in the elongation at the break of all analysed systems, whereas the tensile strength was not affected in a relevant way. Biological assays indicated that electrostatic interactions between the negative charges of the surface of cell membranes and the -NH3+ sites on chitosan chains promoted cell adhesion, while some oxidised species produced during the irradiation process are thought to cause a detrimental effect on the cell viability.

Subpopulations of Circulating Cells with Morphological Features of Malignancy Are Preoperatively Detected and Have Differential Prognostic Significance in Non-Small Cell Lung Cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) frequently presents when surgical intervention is no longer feasible. Despite local treatment with curative intent, patients might experience disease recurrence. In this context, accurate non-invasive biomarkers are urgently needed. We report the results of a pilot study on the diagnostic and prognostic role of circulating tumor cells (CTCs) in operable NSCLC. METHODS: Blood samples collected from healthy volunteers (n = 10), nodule-negative high-risk individuals enrolled in a screening program (n = 7), and NSCLC patients (n = 74) before surgery were analyzed (4 mL) for the presence of cells with morphological features of malignancy enriched through the ISET® technology. RESULTS: CTC detection was 60% in patients, while no target cells were found in lung cancer-free donors. We identified single CTCs (sCTC, 46%) and clusters of CTCs and leukocytes (heterotypic clusters, hetCLU, 31%). The prevalence of sCTC (sCTC/4 mL ≥ 2) or the presence of hetCLU predicted the risk of disease recurrence within the cohort of early-stage (I-II, n = 52) or advanced stage cases (III-IVA, n = 22), respectively, while other tumor-related factors did not inform prognosis. CONCLUSIONS: Cancer cell hematogenous dissemination occurs frequently in patients with NSCLC without clinical evidence of distant metastases, laying the foundation for the application of cell-based tests in screening programs. CTC subpopulations are fine prognostic classifiers whose clinical validity should be further investigated in larger studies.

Circulating Tumor Cells and Metabolic Parameters in NSCLC Patients Treated with Checkpoint Inhibitors.

Circulating tumor cells (CTC) count and characterization have been associated with poor prognosis in recent studies. Our aim was to examine CTC count and its association with metabolic parameters and clinical outcomes in non-small cell lung carcinoma (NSCLC) patients treated with immune checkpoint inhibitors (ICI). For this prospective study, data from 35 patients (23 males, 12 females) were collected and analyzed. All patients underwent an 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) scan and CTC detection through Isolation by Size of Tumor/Trophoblastic Cells (ISET) from peripheral blood samples obtained at baseline and 8 weeks after ICI initiation. Association of CTC count with clinical and metabolic characteristics was studied. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and the log-rank test. Median follow-up was 13.2 months (range of 4.9-21.6). CTC were identified in 16 out of 35 patients (45.7%) at baseline and 10 out of 24 patients at 8 weeks (41.7%). Mean CTC numbers before and after 8 weeks were 15 ± 28 and 11 ± 19, respectively. Prior to ICI, the mean CTC number was significantly higher in treatment-naïve patients (34 ± 39 vs. 9 ± 21, p = 0.004). CTC count variation (ΔCTC) was significantly associated with tumor metabolic response set by European Organization for Research and Treatment of Cancer (EORTC) criteria (p = 0.033). At the first restaging, patients with a high tumor burden, that is, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), had a higher CTC count (p = 0.009). The combination of mean CTC and median MTV at 8 weeks was associated with PFS (p < 0.001) and OS (p = 0.024). Multivariate analysis identified CTC count at 8 weeks as an independent predictor for PFS and OS, whereas ΔMTV and maximum standardized uptake value variation (ΔSUVmax) was predictive for PFS and OS, respectively. Our study confirmed that CTC number is modulated by previous treatments and correlates with metabolic response during ICI. Moreover, elevated CTC count, along with metabolic parameters, were found to be prognostic factors for PFS and OS.

Preliminary data on circulating tumor cells in metastatic NSCLC patients candidate to immunotherapy.

In the current paper, we aimed to investigate circulating tumor cells (CTCs) in non-small cell lung carcinoma (NSCLC) candidates to immunotherapy and correlate findings with clinical and metabolic parameters. Seventeen metastatic NSCLC patients (12 males, 5 females), were prospectively enrolled. All patients underwent 18F-Fluorodeoxyglucose (FDG) PET/CT and CTCs detection before treatment. CTCs isolation by size was carried out with the ISET method. CTCs were characterized based on cytopathological features and were compared with smoking status, histological subtype, pre-immunotherapy treatment, PDL-1 expression, performance status, and semi-quantitative parameters on PET, including SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). We found CTCs in 10 out of 17 patients (59%). Mean number of CTCs was 3 (range 1-7). Only one cell with 3 malignant features was detected in the blood of a healthy control out of 7 (16%). A significantly lower number of CTCs was found in patients previously treated with chemotherapy (P=0.041). No correlation between CTCs and other clinical pathologic characteristics was observed. Patients with an extensive tumor burden, i.e. MTV and TLG, were associated with a higher number of CTCs (P=0.004 and P=0.028, respectively). Likewise, patients with a higher metabolism determined with SUVmean resulted having a higher CTCs count (P=0.048). The presence of CTCs was associated with tumor uptake and metabolic burden on PET/CT, while results were influenced by previous chemotherapy. Whether confirmed in larger series, the combination of the presence of CTCs and FDG PET metabolic parameters might improve prognostic stratification and allow more personalized treatment paradigm.

A prospective randomized study comparing 25-G and 22-G needles of a new platform for endoscopic ultrasound-guided fine needle aspiration of solid masses.

BACKGROUND: A new needle platform for endoscopic ultrasound-guided fine-needle aspiration biopsy has been developed that allows interchangeability of all needle sizes. AIMS: To prospectively compare the efficacy of the new 25-G needles and 22-G needles for obtaining an adequate aspirate of solid masses. METHODS: Randomized controlled trial of 144 patients referred for endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic masses, intraparietal tumours, or lymph-nodes, randomized to the 25-G or 22-G needle arms. RESULTS: An adequate specimen was obtained from 74.3% of cases. The sample tended to be more adequate in the 25-G compared to the 22-G group (81% vs. 68%; p=0.09). Crossover was required in 14 (19%) and 12 (17%) cases in the 22-G and in the 25-G groups, respectively (p=0.7). The overall rate of adequacy improved from 74% before crossover to 90% after crossover (p<0.01). When comparing the two groups after crossover, the rate of obtaining adequate samples was significantly higher in the 25-G arm than in the 22-G arm (95.8% vs. 86.1%; p=0.03). CONCLUSIONS: The 25-G needle was superior to the 22-G needle for endoscopic ultrasound-guided fine-needle aspiration biopsy. The adequacy and diagnostic accuracy improved after crossover, reaching 90%.