Radiogenomics Map-Based Molecular and Imaging Phenotypical Characterization in Localised Prostate Cancer Using Pre-Biopsy Biparametric MR Imaging.

To create a radiogenomics map and evaluate the correlation between molecular and imaging phenotypes in localized prostate cancer (PCa), using radical prostatectomy histopathology as a reference standard. Radiomic features were extracted from T2-weighted (T2WI) and Apparent Diffusion Coefficient (ADC) images of clinically localized PCa patients (n = 15) across different Gleason score-based risk categories. DNA extraction was performed on formalin-fixed, paraffin-embedded (FFPE) samples. Gene expression analysis of androgen receptor expression, apoptosis, and hypoxia was conducted using the Chromosome Analysis Suite (ChAS) application and OSCHIP files. The relationship between gene expression alterations and textural features was assessed using Pearson's correlation analysis. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive accuracy of the model. A significant correlation was observed between radiomic texture features and copy number variation (CNV) of genes associated with apoptosis, hypoxia, and androgen receptor (p-value ≤ 0.05). The identified radiomic features, including Sum Entropy ADC, Inverse Difference ADC, Sum Variance T2WI, Entropy T2WI, Difference Variance T2WI, and Angular Secondary Moment T2WI, exhibited potential for predicting cancer grade and biological processes such as apoptosis and hypoxia. Incorporating radiomics and genomics into a prediction model significantly improved the prediction of prostate cancer grade (clinically significant prostate cancer), yielding an AUC of 0.95. Radiomic texture features significantly correlate with genotypes for apoptosis, hypoxia, and androgen receptor expression in localised prostate cancer. Integration of these into the prediction model improved prediction accuracy of clinically significant prostate cancer.

Radiogenomics Reveals Correlation between Quantitative Texture Radiomic Features of Biparametric MRI and Hypoxia-Related Gene Expression in Men with Localised Prostate Cancer.

OBJECTIVES: To perform multiscale correlation analysis between quantitative texture feature phenotypes of pre-biopsy biparametric MRI (bpMRI) and targeted sequence-based RNA expression for hypoxia-related genes. MATERIALS AND METHODS: Images from pre-biopsy 3T bpMRI scans in clinically localised PCa patients of various risk categories (n = 15) were used to extract textural features. The genomic landscape of hypoxia-related gene expression was obtained using post-radical prostatectomy tissue for targeted RNA expression profiling using the TempO-sequence method. The nonparametric Games Howell test was used to correlate the differential expression of the important hypoxia-related genes with 28 radiomic texture features. Then, cBioportal was accessed, and a gene-specific query was executed to extract the Oncoprint genomic output graph of the selected hypoxia-related genes from The Cancer Genome Atlas (TCGA). Based on each selected gene profile, correlation analysis using Pearson's coefficients and survival analysis using Kaplan-Meier estimators were performed. RESULTS: The quantitative bpMR imaging textural features, including the histogram and grey level co-occurrence matrix (GLCM), correlated with three hypoxia-related genes (ANGPTL4, VEGFA, and P4HA1) based on RNA sequencing using the TempO-Seq method. Further radiogenomic analysis, including data accessed from the cBioportal genomic database, confirmed that overexpressed hypoxia-related genes significantly correlated with a poor survival outcomes, with a median survival ratio of 81.11:133.00 months in those with and without alterations in genes, respectively. CONCLUSION: This study found that there is a correlation between the radiomic texture features extracted from bpMRI in localised prostate cancer and the hypoxia-related genes that are differentially expressed. The analysis of expression data based on cBioportal revealed that these hypoxia-related genes, which were the focus of the study, are linked to an unfavourable survival outcomes in prostate cancer patients.

Urinary bladder recurrences following ureteroscopic biopsies of upper tract urothelial cancers: a multi-centre observational study with genomic assessment for clonality.

BACKGROUND AND AIMS: Urinary bladder recurrences (UBRs) after radical nephroureterectomy (RNUx) are a known challenge in patients with upper-tract urothelial cancers (UTUCs). We aim to assess factors associated with UBR and clonal-relatedness with resected UTUC. METHODS: Patients who underwent RNUx for UTUC between 1998 and 2015 in five institutions were identified. Clonal relatedness between primary UTUC and subsequent UBR in a sub-cohort was assessed using next-generation sequencing. A Kaplan-Meier curve was used to assess differences in UBR between two groups (with or without ureteroscopic biopsy). RESULTS: Of 267 patients with complete records, 73 (27.3%) had UBR during follow-up. The five-year UBR-free survival in all patients was 64.7%. The five-year UBR-free-survival was inferior in patients who underwent URS biopsy compared with patients who did not undergo ureteroscopic biopsy (49.9% vs 76.4%, p < 0.001). History of bladder tumour (HR, 95% CI; 2.94, 1.73-5.00, p < 0.001), ureteroscopic biopsy (HR, 95% CI; 2.21, 1.38-3.53, p = 0.001) and preoperative urine cytology ≥C3 (HR, 95% CI; 2.06, 1.24-3.40, p = 0.005) were independently associated with UBR. Patients with ureteroscopic biopsy (n = 3/5) showed identical mutational changes for common genes (TP53 and FGFR3) between primary UTUC and subsequent UBR. CONCLUSIONS: Ureteroscopic biopsy of UTUC is a significant risk factor for UBR. Qualitative clonality assessment showed identical mutational signatures between primary UTUC and UBR.

Traditional landmark versus ultrasound guided tracheal puncture during percutaneous dilatational tracheostomy in adult intensive care patients: a randomised controlled trial.

INTRODUCTION: Long-term ventilated intensive care patients frequently require tracheostomy. Although overall risks are low, serious immediate and late complications still arise. Real-time ultrasound guidance has been proposed to decrease complications and improve the accuracy of the tracheal puncture. We aimed to compare the procedural safety and efficacy of real-time ultrasound guidance with the traditional landmark approach during percutaneous dilatational tracheostomy (PDT). METHODS: A total of 50 patients undergoing PDT for clinical indications were randomly assigned, after obtaining informed consent, to have the tracheal puncture procedure carried out using either traditional anatomical landmarks or real-time ultrasound guidance. Puncture position was recorded via bronchoscopy. Blinded assessors determined in a standardised fashion the deviation of the puncture off midline and whether appropriate longitudinal position between the first and fourth tracheal rings was achieved. Procedural safety and efficacy data, including complications and number of puncture attempts required, were collected. RESULTS: In total, 47 data sets were evaluable. Real-time ultrasound guidance resulted in significantly more accurate tracheal puncture. Mean deviation from midline was 15 ± 3° versus 35 ± 5° (P = 0.001). The proportion of appropriate punctures, defined a priori as 0 ± 30° from midline, was significantly higher: 20 (87%) of 23 versus 12 (50%) of 24 (RR = 1.74; 95% CI = 1.13 to 2.67; P = 0.006). First-pass success rate was 20 (87%) of 23 in the ultrasound group and 14 (58%) of 24 in the landmark group (RR = 1.49; 95% CI = 1.03 to 2.17; P = 0.028). The observed decrease in procedural complications was not statistically significant: 5 (22%) of 23 in the ultrasound group versus 9 (37%) of 24 in the landmark group (RR = 0.58; 95% CI = 0.23 to 1.47; P = 0.24). CONCLUSIONS: Ultrasound guidance significantly improved the rate of first-pass puncture and puncture accuracy. Fewer procedural complications were observed; however, this did not reach statistical significance. These results support wider general use of real-time ultrasound guidance as an additional tool to improve PDT. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ID: ACTRN12611000237987 (registered 4 March 2011).