Influence of spectral shaping and tube voltage modulation in ultralow-dose computed tomography of the abdomen.

PURPOSE: Unenhanced abdominal CT constitutes the diagnostic standard of care in suspected urolithiasis. Aiming to identify potential for radiation dose reduction in this frequent imaging task, this experimental study compares the effect of spectral shaping and tube voltage modulation on image quality. METHODS: Using a third-generation dual-source CT, eight cadaveric specimens were scanned with varying tube voltage settings with and without tin filter application (Sn 150, Sn 100, 120, 100, and 80 kVp) at three dose levels (3 mGy: standard; 1 mGy: low; 0.5 mGy: ultralow). Image quality was assessed quantitatively by calculation of signal-to-noise ratios (SNR) for various tissues (spleen, kidney, trabecular bone, fat) and subjectively by three independent radiologists based on a seven-point rating scale (7 = excellent; 1 = very poor). RESULTS: Irrespective of dose level, Sn 100 kVp resulted in the highest SNR of all tube voltage settings. In direct comparison to Sn 150 kVp, superior SNR was ascertained for spleen (p ≤ 0.004) and kidney tissue (p ≤ 0.009). In ultralow-dose scans, subjective image quality of Sn 100 kVp (median score 3; interquartile range 3-3) was higher compared with conventional imaging at 120 kVp (2; 2-2), 100 kVp (1; 1-2), and 80 kVp (1; 1-1) (all p < 0.001). Indicated by an intraclass correlation coefficient of 0.945 (95% confidence interval: 0.927-0.960), interrater reliability was excellent. CONCLUSIONS: In abdominal CT with maximised dose reduction, tin prefiltration at 100 kVp allows for superior image quality over Sn 150 kVp and conventional imaging without spectral shaping.

Altered histone acetylation patterns in pancreatic cancer cell lines induce subtype­specific transcriptomic and phenotypical changes.

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at advanced tumor stages with chemotherapy as the only treatment option. Transcriptomic analysis has defined a classical and basal­like PDAC subtype, which are regulated by epigenetic modification. The present study aimed to determine if drug­induced epigenetic reprogramming of pancreatic cancer cells affects PDAC subtype identity and chemosensitivity. Classical and basal­like PDAC cell lines PaTu­S, Capan­1, Capan­2, Colo357, PaTu­T, PANC­1 and MIAPaCa­2, were treated for a short (up to 96 h) and long (up to 30 weeks) period with histone acetyltransferase (HAT) and histone deacetylase (HDAC) inhibitors. The cells were analyzed using gene expression approaches, immunoblot analysis, and various cell assays to assess cell characteristics, such as proliferation, colony formation, cell migration and sensitivity to chemotherapeutic drugs. Classical and basal­like PDAC cell lines showed pronounced epigenetic regulation of subtype­specific genes through acetylation of lysine 27 on Histone H3 (H3K27ac). Moreover, classical cell lines revealed a significantly decreased expression of HDAC2 and increased total levels of H3K27ac in comparison with the basal­like cell lines. Following HAT inhibitor treatment, classical cell lines exhibited a loss of epithelial marker gene expression, decreased chemotherapy response gene score and increased cell migration in vitro, indicating a tumor­promoting phenotype. HDAC inhibitor treatment, however, exerted minimal reprogramming effects in both subtypes. Epigenetic reprogramming of classical and basal­like tumor cells did not have a major impact on gemcitabine response, although the gemcitabine transporter gene SLC29A1 (solute carrier family 29 member 1) was epigenetically regulated.

Immune Cell and Stromal Signature Associated With Progression-Free Survival of Patients With Resected Pancreatic Ductal Adenocarcinoma.

BACKGROUND & AIMS: Changes to the microenvironment of pancreatic ductal adenocarcinomas (PDACs) have been associated with poor outcomes of patients. We studied the associations between composition of the pancreatic stroma (fibrogenic, inert, dormant, or fibrolytic stroma) and infiltration by inflammatory cells and times of progression-free survival (PFS) of patients with PDACs after resection. METHODS: We obtained 1824 tissue microarray specimens from 385 patients included in the European Study Group for Pancreatic Cancer trial 1 and 3 and performed immunohistochemistry to detect alpha smooth muscle actin, type 1 collagen, CD3, CD4, CD8, CD68, CD206, and neutrophils. Tumors that expressed high and low levels of these markers were compared with patient outcomes using Kaplan-Meier curves and multivariable recursive partitioning for discrete-time survival tree analysis. Prognostic index was delineated by a multivariable Cox proportional hazards model of immune cell and stromal markers and PFS. Findings were validated using 279 tissue microarray specimens from 93 patients in a separate cohort. RESULTS: Levels of CD3, CD4, CD8, CD68, and CD206 were independently associated with tumor recurrence. Recursive partitioning for discrete-time survival tree analysis identified a high level of CD3 as the strongest independent predictor for longer PFS. Tumors with levels of CD3 and high levels of CD206 associated with a median PFS time of 16.6 months and a median prognostic index of -0.32 (95% confidence interval [CI] -0.35 to -0.31), whereas tumors with low level of CD3 cell and low level of CD8 and high level of CD68 associated with a median PFS time of 7.9 months and a prognostic index of 0.32 (95% CI 0.050-0.32); we called these patterns histologic signatures. Stroma composition, when unassociated with inflammatory cell markers, did not associate significantly with PFS. In the validation cohort, the histologic signature resulted in an error matrix accuracy of predicted response of 0.75 (95% CI 0.64-0.83; accuracy P < .001). CONCLUSIONS: In an analysis of PDAC tissue microarray specimens, we identified and validated a histologic signature, based on leukocyte and stromal factors, that associates with PFS times of patients with resected PDACs. Immune cells might affect the composition of the pancreatic stroma to affect progression of PDAC. These findings provide new insights into the immune response to PDAC.